Abstract
Introduction
During pulp inflammation, recruited macrophages can differentiate into 2 phenotypes:
proinflammatory M1 and anti-inflammatory M2. Pulp fibroblasts have previously been
shown to regulate pulp inflammation via cytokine and growth factor secretion. We hypothesized
that upon carious injury, pulp fibroblasts interact with macrophages and modulate
their differentiation.
Methods
Cultures of pulp fibroblasts were physically injured and incubated with lipoteichoic
acid (LTA) to mimic the pulp environment underlying a carious lesion. Physical injuries
without LTA were performed on cultured fibroblasts to simulate the surrounding pulp
tissue. Fibroblast supernatants were collected and added to undifferentiated macrophages
to study their differentiation into M1 or M2 phenotypes by investigating cytokine
secretion profiles and phagocytosis capacity. Histologic staining and immunofluorescence
were performed on healthy and carious human tooth sections to localize the 2 macrophage
phenotypes.
Results
LTA-stimulated fibroblasts induced macrophage differentiation into the M1 phenotype
with a significant increase both in tumor necrosis factor alpha secretion and phagocytosis
capacity. By contrast, injured fibroblasts without LTA led to M2 differentiation with
a significant increase in interleukin 10 secretion and low phagocytosis capacity.
In carious teeth, M1 macrophages were detected mainly in the pulp zone underlying
caries, whereas M2 macrophages were detected in the peripheral inflammatory zone.
Conclusions
Fibroblasts induced macrophage differentiation to proinflammatory M1 with high bacteria
phagocytosis capacity to control infection at the carious front. Fibroblasts located
at the periphery of the inflammatory zone induced macrophage differentiation to anti-inflammatory
M2. The fine balance between the 2 phenotypes may represent a prerequisite for initiating
the healing process.
Key Words
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Article info
Publication history
Published online: June 25, 2021
Identification
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© 2021 American Association of Endodontists.
